Molecular Aspects of Taste Perception

Lecture given 10/15/2025

what cell types are in the taste bud?

basal cells, merkel-like basal cell, dark cell, light cell, intermediate cell

basal cell

undifferentiated

merkel-like basal cell

type IV

dark cell

type I

light cell

type I

intermediate cell

type III

what is the function of type II cells?

taste receptors but no synaptic contact- they send signals to type III 

what is the function of type III cells?

receive signals from type II cells and then release neurotransmitters serotonin and ATP

what is the function of type IV cells?

release serotonin and has synaptic contacts

what is the function of type I cells?

control intercellular fluid ionic make-up (Na+ and K+ levels)

sweet

carbhydrates (sucrose, glucose) and some amino acids (aspartame)

salty

monovalent cations (sodium, potassium)

bitter

many different chemicals, some are toxic

sour

acids and low pH

umami (savory)

amino acids or peptide taste enhancers like monosdium glutamate

t/f certain parts of the tongue taste certain flavors

false- all areas of the tongue express all known receptors, so all flavors can probably be detected everywhere to some degree

why is it important to identify taste receptors?

taste blindess happens but treatment is possible if we understand the molecular and cellular physio

nutritional problems could be addressed

taste receptors are chemosensors for nutrients/toxins elsewhere

what happens immediately after an animal tastes a sweet substance?

adenylate cyclase and cAMP are increased in tongue epithelium

what is a blocking compond that blocks the ability to taste sweet substances by acting as a competitive inhibitor?

4,6-dichloro-4,6-dideoxy-alpha-D-galactopyranoside

after adenylate cyclase and cAMP increase from sweet taste sensation, what changes happen next?

calcium is released from intracellular stores

potassium channel ions close

sodium channels open leading to Na+ uptake

action potentials occur

neurotransmitters are released, activating adjacent nerves that lead to the brain

what is the cell physiology of sweet and bitter taste perception characterized by?

cAMP increase, intracellular calcium stores releasing, action potentials and neurotransmitter release

t/f cAMP blocks potassium channels which is what causes an action potential to be generated when sweet/bitter taste receptors are activated

true

cAMP increases depends on…

g protein coupled receptors

when a g protein is bound to GDP, is it active or inactive?

inactive

when a g protein is bound to GTP, is it active or inactive?

active

t/f receptor proteins and g proteins are separate but they work together

true

t/f g proteins are not unique

false- they are unique but do have common regions like GDP/GTP binding domains

gustducin knock out mice

mice no longer avoided bitter substances, diminished responsiveness to sweets, no alterations to responsiveness to sour or salty, diminished action potential of taste cells in response to bitter and sweet substances

how were taste receptors first identified?

cDNA libraries made from taste cell RNAs were screen for mRNAs containing the common features of the G protein receptor class

T1R1 and T1R2 were not always co-expressed with gustducin but otherwise were expressed by taste cells in a way that is consistent with being taste cell receptors

where are TR1R1 and TR1R2 located?

at or near the taste pore opening

what human chromosome has inherited taste blindess been linked to?

chromosome 5- contains putative G protein receptor in the right region of this chromosome

where are the genetics of T2R receptors located?

chromosomes 5, 12, and 7 (and 6 in mice)

how many estimated putative G protein coupled taste receptor genes are there in the human genome?

100 related genes

where are most T2R receptors located in a mouse?

geschmackstreifen (german for taste strip, looks like a mouse ‘palate’), epiglottis, foliate papillae, circumvallate papilla

NOT fungiform papillae

T2Rs are expressed in the same taste cells as…

gustducin

what is the only sweet taste receptor?

T1R2 + T1R3 dimer

different sweet tastants bind to different domains of the receptor, each activating the receptor

how many bitter taste receptor genes are there in the T2R family?

30

each receptor homo and heterodimer recognizes different kinds of bitter tastants

what is the taste receptor for umami?

T1R1 + T1R3 dimer

recognizes MSG and other amino acids

is there a sour taste receptor?

no- PKD2L1 senses low pH as it is a hydrogen ion channel but may contribute to tasting sour

what is the salt taste receptor and how does it work?

TRPV1t

works by increasing intracellular calcium release, activating protein kinase C and PI3 kinase

has a structure consistent with an ion channel

t/f mouse have an additional salt aversion receptor

true- ENaC, inhibited by amiloride

OTOP1

protein channel that permits Zn2+ uptale which inhibits sour taste perception

what permits you to taste beer, champagne, and carbonated beverages?

carbonic anhydrase 4

how does carbonic anhydrase work?

produces protons from carbon dioxide which are detected by PKD2L or maybe OTOP1

is taste more likely following the labeled line model or the in line tase perception model?

in line taste perception model

what is the evidence for labeled in line taste perception?

substitution of the ligand binding domain of taste receptor cells in sweet taste cells to that the cells would now recognize a bitter compound resulted in the mouse liking the bitter compound

what do bitter and sweet taste receptors in the gut do?

when activated they release gastric hormones that control appetite and cellular metabolism (GLP-1, GIP, ghrelin, CCK) and glucose transporters to regulate absorption of sugars from food

GLP-1 and GIP

basis for weight loss drugs

incretins, gut derived hormones that stimulate insulin release from the pancreas after a meal

ghrelin

stimulates hunger

CCK

short term appetite suppressant

what causes loss of taste and smell in covid patients?

inflammation after infection

t/f there are bitter taste receptors in the ciliated airway epithelial cells and they co-localize with acetylated tubulin

true

what happens if a bitter taste receptor is activated in the airway?

T2R1s/gustducin/phospholipase C activation by intratracheal administration of receptor agonists results in slower breathing in mice

sweet taste receptor activation turn off those effects

polymorphisms

naturally occurring inherited sequence variation in genes

can account for differences among individuals with respect to bitter taste perception of specific compounds, sensitivity to specific airborne toxins or allergens, or therapeutic opportunities

nutrient sensing in the gut by T1R2/T1R3 and GPR120 is followed by…

increased secretion of appetite suppressing hormones GLP-1, PYY, and GIP

what limits absorption of nutrients in the gut?

T2Rs

t/f other organs (beside pancreas) also respond to incretins and are negatively affected by diabetes

true

thaumatin

2000-3000x sweeter than sucrose, derived from the fruit of the katemfe plant in west africa

monellin

found in the fruit of the west african shrub the serendipity berry

miraculin

found in the berries of the miracle fruit plant

brazzein

from the oubli fruit found in west africa, 500-2000x sweeter than sucrose, heat stable, and highly soluble

what are the advantages of sweet proteins over sugars?

digestion of sweet proteins have zero or neutral impact on blood sugar, insulin levels, or gut microbiome

zero calorie

what are the great things about brazzein?

no impact on the gut microbiome, digests like a protein, has antioxidant, anti-inflammatory, and anti-allergic properties

at a neutral pH, miraculin has…

no effect on taste perception or a slight inhibition of taste perception

it binds to the sweet taste receptor but does not activate signaling, it will inhibit the binding of sugars

at low pH, miraculin has…

an agonist (stimulatory) effect on sweet taste signaling

t/f some tate receptors are expressed in non-oral tissues and have physiological roles unrelated to taste perception

true